ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ObjectiveAge-related macular degeneration （AMD） is one of the leading causes of low vision and blindness in people over 50 years old， and dry AMD （dAMD） is one type for which there is currently no clear treatment. On the basis of the diagnosis and clinical characteristics of dAMD in traditional Chinese and Western medicine， this paper evaluated the fitting degrees of existing animal models of dAMD with clinical characteristics according to the evaluation methods of animal models， and put forward suggestions and prospects. MethodsLiterature on animal models of dAMD was searched against database， and the characteristics of the models were assigned according to the diagnosis criteria of diseases and syndromes of traditional Chinese and Western medicine， and the fitting degrees of the models with clinical characteristics were analyzed and evaluated. ResultsAt present， the animal models of dAMD are mainly established targeting complement factors， chemokines， oxidative damage， lipid/glucose metabolism， and natural strains. Most of the models can simulate the major pathological changes of dAMD， showing the fitting degree of 25%-50% with clinical characteristics in Western medicine. However， the evaluation of traditional Chinese medicine （TCM） syndromes， especially the evaluation of secondary syndromes， is missing， and the models present low fitting degrees with the clinical characteristics in TCM. ConclusionExisting animal models of dAMD are mostly established under the guidance of Western diagnostic standards， which reproduce the main disease characteristics of Western medicine and lack observation of TCM syndromes. Future studies can pay attention to the intervention factors and evaluation systems of spleen deficiency Qi deficiency and liver-kidney Yin deficiency syndrome and build the animal model of dAMD with integration of disease and syndrome based on clinical characteristics of traditional Chinese and Western medicine.

ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective To analyze the current status of health resources and medical service utilization in children's hos-pitals in China in 2022,explore existing challenges,and propose targeted solutions.Methods This study evaluated the develop-ment of health resources and service utilization patterns in children's hospitals based on 2022 data.Results Children's hospi-tals exhibited a"dumbbell-shaped"structure in bed capacity distribution,with severe polarization between small-scale and large-scale facilities.Insufficient human resources and excessive workloads were prominent,particularly for physicians.Additionally,outpatient services faced high pressure,while inpatient resources were underutilized.Conclusion To address these issues,we recommend optimizing the hierarchical diagnosis and treatment system by leveraging medical consortiums for resource allocation,enhancing pediatric physician training and adopting technology to alleviate workloads,and improving inpatient service models with dynamic resource allocation to address seasonal demand fluctuations.

[Objective]To clearly identify the difference between rescue injuries and agonal injuries and to avoid duplicate identifications and misidentifications.[Methods]Based on the forensic pathological data of 5 923 cases of death cause identification from 2013 to 2022 in Sun Yat-sen University Forensic Identification Center and Guangzhou Tianhe District Branch of Guangzhou Public Security Bureau,this study retrospectively studied the characteristics of rescue injuries and agonal injuries seen in cause of death identification and their influence on cause of death identification.[Results]Among all the 5 923 cases,640 cases were found to have rescue injuries or agonal injuries,and 624 cases received treatment,of which 609 cases were found to have rescue injuries(97.60%),44 cases were found to have agonal injuries,and 13 cases were found to have both types of injuries.Among the 640 cases,441 were male and 199 were female.The age of death was discontinuously distributed from 0 to 95 years old.The leading cause of death was disease,followed by mechanical injury and asphyxia.The main manifestations of rescue injuries were rib and sternum fractures,soft tissue injuries in the prechest area or face,and pericardial rupture.The most common injuries in agonal stage were falling after unconsciousness,inhalation of foreign body in respiratory tract or multiple violent injuries.Among the 640 cases,19 cases were repeatedly identified,including 15 cases of rescue injuries,6 cases of agonal injuries,and 2 cases of both types of injuries.Compared with the cases where neither type of injuries was detected,the repeated identification rate of treatment injuries and agonal injuries was significantly increased(χ2=4.04,P=0.044;χ2=43.49,P<0.001).Among the 640 cases,11 cases(1.72%)were misidentified as the initial injuries in the first identification,and 13 cases had combined rescue injuries or agonal injuries that were involved in death.[Conclusions]By elucidating the epidemiological characteristics of the two types of injuries,this study proved that the two types of injuries were associated with higher rates of repeated identification and misidentification,which provided a reference for reducing repeated identification and misidentification and improving the accuracy of cause of death identification.

Objective To analyze the current status of health resources and medical service utilization in children's hos-pitals in China in 2022,explore existing challenges,and propose targeted solutions.Methods This study evaluated the develop-ment of health resources and service utilization patterns in children's hospitals based on 2022 data.Results Children's hospi-tals exhibited a"dumbbell-shaped"structure in bed capacity distribution,with severe polarization between small-scale and large-scale facilities.Insufficient human resources and excessive workloads were prominent,particularly for physicians.Additionally,outpatient services faced high pressure,while inpatient resources were underutilized.Conclusion To address these issues,we recommend optimizing the hierarchical diagnosis and treatment system by leveraging medical consortiums for resource allocation,enhancing pediatric physician training and adopting technology to alleviate workloads,and improving inpatient service models with dynamic resource allocation to address seasonal demand fluctuations.

Objective To observe the effects of acupuncture at acupoints along the meridians on the expression of frontal lobe associated protein kinase in pchlorophenylalanine(PCPA)induced insomnia rats;To explore the mechanism of acupuncture in improving insomnia.Methods Totally 60 rats were randomly divided into blank group,model group,sham acupuncture group,acupuncture group and Western medicine group,with 12 rats in each group.An insomnia model rat was induced by intraperitoneal injection of PCPA.The acupuncture group received acupuncture at"Baihui","Shenmen"(bilateral),and"Sanyinjiao"(bilateral),while the sham acupuncture group only fixed the needle at the corresponding acupoints but did not penetrate the skin,while the model group was only fixed for 30 minutes,the Western medicine group was given a solution of estazolam by gavage for 7 consecutive days,the blank group was not treated.The pentobarbital sodium reversal experiment was used to detect the sleep latency and sleep time of rats,ELISA was used to detect the content of melatonin(MT)in plasma,RT-PCR was used to detect the mRNA expressions of calmodulin dependent protein kinase(CaMK)Ⅱ,protein kinase C(PKC)and p38 mitogen activated protein kinase(MAPK)in frontal lobe tissue,and Western blot was used to detect the protein expressions of CaMKⅡ,PKC and p38MAPK in frontal lobe tissue.Results Compared with the blank group,the sleep latency of the model group rats were significantly prolonged and the sleep time were significantly shortened(P<0.01),the content of MT in plasma was significantly reduced(P<0.01),and the mRNA and protein expressions of CaMKⅡ and PKC in frontal lobe tissue were significantly decreased(P<0.01),the mRNA and protein expressions of p38MAPK were significantly increased(P<0.01).Compared with the model group,the sleep latency were significantly shortened and the sleep time were significantly prolonged in the acupuncture group and the Western medicine group(P<0.01),the plasma MT content significantly increased(P<0.01),the mRNA and protein expressions of CaMKⅡ and PKC in frontal lobe tissue significantly increased(P<0.05),and the mRNA and protein expression of p38MAPK significantly decreased(P<0.01).Compared with the sham acupuncture group,the sleep latency shortened and sleep time were significantly prolonged in the acupuncture group and the Western medicine group(P<0.01),plasma MT content significantly increased(P<0.01),PKC mRNA expression in frontal lobe tissue significantly increased(P<0.01),and p38MAPK mRNA expression significantly decreased(P<0.01).There was no statistically difference in various indicators between the acupuncture group and the Western medicine group(P>0.05).Conclusion Acupuncture at acupoints along the meridians can shorten the sleep latency and prolong sleep time,improve sleep status by regulating the expression of associated protein kinase in frontal lobe of insomnia rats.

Breast cancer has been the second most common solid tumor that metastasizes to the central nervous system after lung cancer.Triple-negative breast cancer(TNBC)has an earlier occurrence and high incidence of brain metastasis with its associated poor prognosis and limited treatment options due to the presence of the blood-brain barrier and lack of targeted drugs.Local treatment,including surgery and radiation therapy,are still the main therapy for brain metastasis.Surgical resection can not only relieve neurologic impairment of brain metastasis patients,but also can clarify the pathological type.Moreover,surgical resection combined with radiotherapy can improve the prognosis of brain metastasis patients compared to surgery or radiotherapy alone.By now,whole-brain radiation therapy(WBRT)is still considered the gold standard for multiple brain metastases,and meningeal metastases,but it will lead to neurocognitive decline,so hippocampal avoidance is essential.For selected patients with oligometastases,stereotactic radiotherapy has replaced WBRT to reduce cognitive toxicity.However,local treatment of TNBC brain metastasis cannot control the progress of brain metastasis and has significant side effects,so systemic therapy is needed.Chemotherapy drugs such as capecitabine and cisplatin can penetrate the blood-brain barrier,but their efficacy is limited.Therefore,the research and development of new targeted drugs and the exploration of new targets are necessary for TNBC brain metastasis.Research has found that patients carrying germline BRCA1/2 mutations have a higher risk of brain metastasis.Currently,the poly adenosine diphosphate ribose polymerase(PARP)inhibitor demonstrated antitumor activity in patients with advanced breast cancer and a germline BRCA1/2 mutation,and it can penetrate the blood-brain barrier.The phase Ⅲ trial EMBRACA reported that the PARP inhibitor talazoparib can prolong the progression-free survival of TNBC patients with brain metastasis.In addition,antibody drug conjugates(ADCs)trastuzumab deruxtecan(T-DXd)can also penetrate the blood-brain barrier.Studies such as DEBBRAH have shown that T-DXd has significant therapeutic effects in HER2 positive brain metastasis patients,while research on HER2 low expression patients has not yet reached the endpoint,and its role in TNBC brain metastasis is worth looking forward to.Sacituzumab govitecan(SG)is also an ADC composed of an antibody targeting the human trophoblast cell-surface antigen 2.The phase Ⅲ ASCENT study showed that in the full population(including 61 patients with brain metastasis),SG could significantly prolong the progression-free survival of advanced TNBC patients compared to the patients who received chemotherapy.ANG1005,a novel taxane derivative,can cross the blood-brain barrier as well.A multicenter,open-label phase Ⅱ study revealed that ANG1005 could prolong overall survival of patients with brain metastasis.In addition,phosphoinositide3-kinase,(PI3K)/protein kinase(AKT)/mammalian target of rapamycin(mTOR)pathway inhibitors,fatty acid synthase inhibitors,and the drugs with new delivery systems have become potential treatment options for TNBC brain metastasis patients.Although the Impassion 130 reported that no benefit trend for immunotherapy in TNBC brain metastasis,basic research has shown that radiotherapy combined with immunotherapy has a synergistic effect.Currently,multiple clinical trials(NCT03483012,NCT03449238,etc.)are exploring the efficacy of radiotherapy combined with immunotherapy in brain metastasis,and the results are promising.This article reviewed the research progress of TNBC brain metastasis treatment.

Organ transplantation has become an effective treatment for multiple end-stage diseases. However, the recipients of organ transplantation need to take immunosuppressive drugs for a long time after operation, which leads to low immune function and relatively high incidence of bacterial, viral and fungal infections. Traditional microbial detection methods, such as pathogen culture, immunological detection and polymerase chain reaction, have been widely applied in infection detection, whereas these methods may cause problems, such as long detection time and presumed pathogens. Metagenomic next-generation sequencing has been widely adopted in infection prevention and control in organ transplantation in recent years due to high detection rate and comprehensive detection of pathogen spectrum. In this article, the application of metagenomic next-generation sequencing in the prevention and control of infection in solid organ transplantation was reviewed, aiming to provide reference for the diagnosis and treatment of transplantation-related infection.